51 research outputs found
Evolution of the Hemifused Intermediate on the Pathway to Membrane Fusion
AbstractThe pathway to membrane fusion in synthetic and biological systems is thought to pass through hemifusion, in which the outer leaflets are fused while the inner leaflets engage in a hemifusion diaphragm (HD). Fusion has been proposed to be completed by lysis of the expanded HD that matures from a localized stalklike initial connection. However, the process that establishes the expanded HD is poorly understood. Here we mathematically modeled hemifusion of synthetic vesicles, where hemifusion and fusion are most commonly driven by calcium and membrane tension. The model shows that evolution of the hemifused state is driven by these agents and resisted by interleaflet frictional and tensile stresses. Predicted HD growth rates depend on tension and salt concentration, and agree quantitatively with experimental measurements. For typical conditions, we predict that HDs expand at ∼30 μm2/s, reaching a final equilibrium area ∼7% of the vesicle area. Key model outputs are the evolving HD tension and area during the growth transient, properties that may determine whether HD lysis occurs. Applying the model to numerous published experimental studies that reported fusion, our results are consistent with a final fusion step in which the HD ruptures due to super-lysis HD membrane tensions
Irreversibility and Polymer Adsorption
Physisorption or chemisorption from dilute polymer solutions often entails
irreversible polymer-surface bonding. We present a theory of the
non-equilibrium layers which result. While the density profile and loop
distribution are the same as for equilibrium layers, the final layer comprises
a tightly bound inner part plus an outer part whose chains make only fN surface
contacts where N is chain length. The contact fractions f follow a broad
distribution, P(f) ~ f^{-4/5}, in rather close agreement with strong
physisorption experiments [H. M. Schneider et al, Langmuir v.12, p.994 (1996)].Comment: 4 pages, submitted to Phys. Rev. Let
The Ultrasensitivity of Living Polymers
Synthetic and biological living polymers are self-assembling chains whose
chain length distributions (CLDs) are dynamic. We show these dynamics are
ultrasensitive: even a small perturbation (e.g. temperature jump) non-linearly
distorts the CLD, eliminating or massively augmenting short chains. The origin
is fast relaxation of mass variables (mean chain length, monomer concentration)
which perturbs CLD shape variables before these can relax via slow chain growth
rate fluctuations. Viscosity relaxation predictions agree with experiments on
the best-studied synthetic system, alpha-methylstyrene.Comment: 4 pages, submitted to Phys. Rev. Let
Non-Equilibrium in Adsorbed Polymer Layers
High molecular weight polymer solutions have a powerful tendency to deposit
adsorbed layers when exposed to even mildly attractive surfaces. The
equilibrium properties of these dense interfacial layers have been extensively
studied theoretically. A large body of experimental evidence, however,
indicates that non-equilibrium effects are dominant whenever monomer-surface
sticking energies are somewhat larger than kT, a common case. Polymer
relaxation kinetics within the layer are then severely retarded, leading to
non-equilibrium layers whose structure and dynamics depend on adsorption
kinetics and layer ageing. Here we review experimental and theoretical work
exploring these non-equilibrium effects, with emphasis on recent developments.
The discussion addresses the structure and dynamics in non-equilibrium polymer
layers adsorbed from dilute polymer solutions and from polymer melts and more
concentrated solutions. Two distinct classes of behaviour arise, depending on
whether physisorption or chemisorption is involved. A given adsorbed chain
belonging to the layer has a certain fraction of its monomers bound to the
surface, f, and the remainder belonging to loops making bulk excursions. A
natural classification scheme for layers adsorbed from solution is the
distribution of single chain f values, P(f), which may hold the key to
quantifying the degree of irreversibility in adsorbed polymer layers. Here we
calculate P(f) for equilibrium layers; we find its form is very different to
the theoretical P(f) for non-equilibrium layers which are predicted to have
infinitely many statistical classes of chain. Experimental measurements of P(f)
are compared to these theoretical predictions.Comment: 29 pages, Submitted to J. Phys.: Condens. Matte
Myosin turnover controls actomyosin contractile instability
Actomyosin contractile force produced by myosin II molecules that bind and pull actin filaments is harnessed for diverse functions, from cell division by the cytokinetic contractile ring to morphogenesis driven by supracellular actomyosin networks during development. However, actomyosin contractility is intrinsically unstable to self-reinforcing spatial variations that may destroy the actomyosin architecture if unopposed. How cells control this threat is not established, and while large myosin fluctuations and punctateness are widely reported, the full course of the instability in cells has not been observed. Here, we observed the instability run its full course in isolated cytokinetic contractile rings in cell ghosts where component turnover processes are absent. Unprotected by turnover, myosin II merged hierarchically into aggregates with increasing amounts of myosin and increasing separation, up to a maximum separation. Molecularly explicit simulations reproduced the hierarchical aggregation which precipitated tension loss and ring fracture and identified the maximum separation as the length of actin filaments mediating mechanical communication between aggregates. In the final simulated dead-end state, aggregates were morphologically quiescent, including asters with polarity-sorted actin, similar to the dead-end state observed in actomyosin systems in vitro. Our results suggest the myosin II turnover time controls actomyosin contractile instability in normal cells, long enough for aggregation to build robust aggregates but sufficiently short to intercept catastrophic hierarchical aggregation and fracture
Morphology selection of nanoparticle dispersions by polymer media
A systematic theory of ultrathin polymer films as organizing media to achieve 2D nanoparticle arrangements was developed. The key physical variables to achieve nanoparticle dispersions and control morphology were determined.open727
Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices
Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied via local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces by plating cells on sub-micron elastomeric pillars. We found that actomyosin-based sarcomere-like contractile units (CUs) simultaneously moved opposing pillars in net steps of ~2.5 nm, independent of rigidity. What correlated with rigidity was the number of steps taken to reach a force level that activated recruitment of α-actinin to the CUs. When we removed actomyosin restriction by depleting tropomyosin 2.1, we observed larger steps and higher forces that resulted in aberrant rigidity sensing and growth of non-transformed cells on soft matrices. Thus, we conclude that tropomyosin 2.1 acts as a suppressor of growth on soft matrices by supporting proper rigidity sensing
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